Serotonin and histamine storage in mast cell secretory granules is dependent on serglycin proteoglycan

BackgroundSerotonin and histamine are components of human and rodent mast cell secretory granules.ObjectiveSerotonin and histamine are stored in the same compartment as serglycin proteoglycan. Here we addressed the possibility that serglycin may be involved in their storage and/or release.MethodsThe storage and release of histamine and serotonin was studied in bone marrow–derived mast cells (BMMCs) and in peritoneal mast cells from wild-type or serglycin–/– mice.ResultsBoth serotonin and histamine storage in BMMCs was positively correlated with the degree of mast cell differentiation, and the amount of stored amine was reduced in serglycin–/– BMMCs compared with wild-type controls. The amounts of histamine/serotonin stored were reflected by the expression levels of histidine decarboxylase and tryptophan hydroxylase 1, respectively. Calcium ionophore activation resulted in serotonin/histamine release both from wild-type and serglycin–/– BMMCs. Interestingly, serotonin release was induced in cells lacking intracellular stores of serotonin, suggesting de novo synthesis. The knockout of serglycin affected the levels of stored and released mast cell serotonin and histamine to an even larger extent in in vivo–derived mast cells than in BMMCs.ConclusionThese results establish a previously assumed, but not proven, role of serglycin in storage of histamine and, further, establish for the first time that serotonin storage in mast cells is dependent on serglycin proteoglycan.